Official WPI response to the Singh study

While WPI researchers continue to review the data presented by Dr. Singh, we believe that it is important to correct and clarify information regarding this study. Several individuals were consented to participate in this study as positive controls to enable Dr. Singh to develop assays to detect multiple variants of XMRV. Of these, only three were from the original Lombardi et al. cohort, two of whom were among those positive for a XMRV. A XMRV was isolated from one of those patient's PBMCs, cloned and fully sequenced (GenBank accession number GQ 497343 as identified in the NIH genetic sequence database). Sequence data demonstrates that this virus is clearly distinct from XMRV (vp62) and 22Rv1. A budding virus particle from that sample was pictured in an electron micrograph in Lombardi et al. Virus from that patient sample was also transmitted both from the PBMCs and plasma
to an uninfected indicator cell line, LNCaP. Finally, these results were supported by a separate lab using serological methods as reported by Lombardi et al.

Twelve additional samples from individuals not included in the Lombardi et al. study were independently collected by a third party and sent directly to Dr. Singhs lab. Some of these subjects were positive for highly related sequences, including the polytropic and modified polytropic sequences identified by Lo et al., as determined by the WPI prior to the publication of the Singh study. Many of those subjects were also positive for ENV antibodies to a XMRV (vp62 and other XMRV family members), indicating that these patients had an immune response to a XMRV.

In addition, WPI investigators and others have provided evidence of sequence diversity between a XMRV (vp62), other similar XMRVs detected by WPI (designated internally with a number corresponding to a clinical isolate), a XMRV (p variant), and other related human gamma retroviruses. Therefore, we believe that it is vitally important that investigators interested in furthering the understanding of blood borne XMRV as a human pathogen use a proven positive clinical isolate as the control when developing tests to detect this newly discovered human retrovirus.

WPI and the U.S. clinical laboratory performing XMRV tests pursuant to a license agreement with WPI have extensive controls in place to prevent and detect contamination. Approximately three thousand tests have been performed on patient samples to date using clinically validated tests; about one third have been found to be positive. Multiple sequences from these three thousand samples have been submitted to GenBank and are awaiting publication. It is critical, in light of these findings, that all treatment decisions are left to physicians and their patients, including the use of antiretrovirals.

While WPI researchers acknowledge that there is still much to be learned about the lifecycle and in vivo reservoirs of this family of human gamma retroviruses, we remain confident in the results reported in Science by Lombardi et al. Most importantly, we are committed to human gamma retroviral research in neuro-immune disease and will continue to offer our help to the medical and scientific community when requested.

I've never really like the WPI's approach to PR, and it seems even more out of place now. Oh well... it doesn't really matter. If they don't identify blinded samples with the BWG and Lipkin, they were over anyway, so I guess there's no need to be cautious now.

Your quote chopped some of it off. Here are the last two paragraphs in full:

WPI and the U.S. clinical laboratory performing XMRV tests pursuant to a license agreement with WPI have extensive controls in place to prevent and detect contamination. Approximately three thousand tests have been performed on patient samples to date using clinically validated tests; about one third have been found to be positive. Multiple sequences from these three thousand samples have been submitted to GenBank and are awaiting publication. It is critical, in light of these findings, that all treatment decisions are left to physicians and their patients, including the use of antiretrovirals.

While WPI researchers acknowledge that there is still much to be learned about the lifecycle and in vivo reservoirs of this family of human gamma retroviruses, we remain confident in the results reported in Science by Lombardi et al. Most importantly, we are committed to human gamma retroviral research in neuro-immune disease and will continue to offer our help to the medical and scientific community when requested.

Click to expand...

Basically, the first paragraph shows that there are many lines of evidence to suggest that one of the WPI samples was truly positive for XMRV. Electron micrograph (done by Singh herself, I believe), actual sequencing of it's isolate (and it's distinct from VP62, which Singh calibrated to), serological evidence from a different lab, and infectivity. This paragraph casts doubt on the ability of Singh's assays to detect clinical XMRV since they couldn't detect it in this sample. The fact that there are many lines of evidence supporting positivity of this sample makes it much harder to argue "but how do we know it's actually positive?" Because there is a picture of it that you took yourself Dr. Singh!

The second and third paragraphs touch upon further serological evidence and sequence diversity (likely missed in the Singh study which optimized assays to detect VP62).

Lastly, they note that there are multiple new isolated sequences pending publication in GenBank. The diversity of these sequences, once published, could go a long way toward explaining many of the negative studies. We'll have to wait and see, though.

I've never really like the WPI's approach to PR, and it seems even more out of place now. Oh well... it doesn't really matter. If they don't identify blinded samples with the BWG and Lipkin, they were over anyway, so I guess there's no need to be cautious now.

Click to expand...

Would you care to expand on this? You don't like that they don't use their inner voice? Is that it?

Yeah - and surely Singh realises this! The WPI keep talking like they have overwhelming evidence on their side, but it seems like increasingly few scientists agree with them.

Combined with innuendo like "it is vitally important that investigators interested in furthering the understanding of blood borne XMRV", it makes the WPI seem increasingly out of touch with the mainstream. That's fine for a short time... if you've got killer evidence about to be published... but it's been 18 months now. If they really had such a water-tight case, should they not be able to get it through peer review in that time?

The uncertainty around CFS leaves a lot of room for people to form their own beliefs, and then become committed to them. I'm sure we've all seen this happen, to patients and doctors. I still think it's possible that the WPI is right about XMRV and CFS, but the way they're engaging with their critics reminds me of the faith based approach CFS has had far too much of. Hopefully their faith will be well placed, but I would prefer a more cautious and careful approach.

Yeah - and surely Singh realises this! The WPI keep talking like they have overwhelming evidence on their side, but it seems like increasingly few scientists agree with them.

Combined with innuendo like "it is vitally important that investigators interested in furthering the understanding of blood borne XMRV", it makes the WPI seem increasingly out of touch with the mainstream. That's fine for a short time... if you've got killer evidence about to be published... but it's been 18 months now. If they really had such a water-tight case, should they not be able to get it through peer review in that time?

The uncertainty around CFS leaves a lot of room for people to form their own beliefs, and then become committed to them. I'm sure we've all seen this happen, to patients and doctors. I still think it's possible that the WPI is right about XMRV and CFS, but the way they're engaging with their critics reminds me of the faith based approach CFS has had far too much of. Hopefully their faith will be well placed, but I would prefer a more cautious and careful approach.

Click to expand...

I think they've been pariahs for a long time now. I kind of like the winner take all approach. The WPI will either be spectacular heroes or spectacular goats. I find that refreshing in this era where there is more spin than substance.

Wow. Singh found a false negative in at least one of the samples. That we can be sure of. Singh took a picture with an electron microscope of the budding virus. So her assays used to detect XMRV did not work, in this case.

I thought the response from WPI was thoughtful and professional. They didn't disparage Singh or her study. They brought out the information that they believe will help researchers find XMRV and other variants. They need to use a positive clinical isolate to calibrate their assays, if they are really wanting to find the retrovirus. Seems like common sense.

Wow. Singh found a false negative in at least one of the samples. That we can be sure of. Singh took a picture with an electron microscope of the budding virus. So her assays used to detect XMRV did not work, in this case.

Click to expand...

From what I've read, the budding virus could have been something other than XMRV, and virologists don't really see it as a key bit of evidence. I don't think we can assume Singh failed to take account of evidence from Singh.

re Winner takes all: Yeah - it doesn't really make much difference now. If they'd played it differently, then even if XMRV hadn't worked out htey could have still been in a good position to continue with CFS research. Now, it's difficult to imagine that happening.

From what I've read, the budding virus could have been something other than XMRV, and virologists don't really see it as a key bit of evidence. I don't think we can assume Singh failed to take account of evidence from Sing

Click to expand...

Could you provide a link to what you read that discounts this important piece of evidence, please?

Hi eric,
Yes, I noticed that bit as well... That's what I've been waiting for... I wondered what they were doing with the info about their sequences...

And here's another interesting bit that I noticed:

In addition, WPI investigators and others have provided evidence of sequence diversity between a XMRV (vp62), other similar XMRVs detected by WPI (designated internally with a number corresponding to a clinical isolate), a XMRV (p variant), and other related human gamma retroviruses.

Multiple sequences from these three thousand samples have been submitted to GenBank and are awaiting publication.

Click to expand...

yes, that part is fantastic. That should really help get to the bottom of all this. I've been waiting to hear this.

I have to tentatively agree with critics that you can't use a positive clinical sample to determine whether, in fact, the clinical patients are indeed positive. I admit that I don't know how these things have been done in the past, but it doesn't make any sense to me, to use the thing you want to be testing, as a positive control. It doesn't make a lot of sense to use XMRV from prostate cancer, either, though, so there don't seem to be any good options.

However I also agree that Singh's results do not say anything definite about the Lombardi and Lo papers. It would again be anecdotal to apply her results to other papers (even though she's a far better virologist than the others who reported finding contamination).

The plain fact is, we don't know anything one way or the other at this point. We need more high-quality research, hopefully more in addition to the BWG study, and I hope we get it.

Combined with innuendo like "it is vitally important that investigators interested in furthering the understanding of blood borne XMRV", it makes the WPI seem increasingly out of touch with the mainstream. That's fine for a short time... if you've got killer evidence about to be published... but it's been 18 months now. If they really had such a water-tight case, should they not be able to get it through peer review in that time?

Click to expand...

The way I understand the situation is that no journals will publish Judy Mikovits' work, just because her name is associated with it. (i.e. it's too hot to publish - too controversial.)

That's partly why Lombardi has taken over Mikovits' previous role at the WPI - so they can get their research work published.

Real scientific. Sounds like a high school clique in charge of what goes in the Senior Class Yearbook. But I guess "that's how science works". End of sarcasm.

Click to expand...

Yes, my guess is that there has been a cliquey smear campaign against Judy within the scientific establishment.
They probably see her as a problematic trouble maker who dares to test and challenge established scientific ways of thinking.
I imagine it's a bit of an old boys network within the scientific journals as well.

Multiple sequences from these three thousand samples have been submitted to GenBank and are awaiting publication.......

That's the best news this year!!

Click to expand...

Yes it's great news, but don't forget that Switzer of the CDC has recently published a paper that establishes that XMRV is a human virus, with no possibility of it being either a mouse contaminant or a contaminant from a cell line, and he has sequenced 3 entirely new strains... I thought that was actually better news than this news... The CDC confirming that XMRV is a human virus, and that it has barely detectable, extremely low copy numbers in prostate tissue and is extremely hard to detect in the blood... I never thought I'd see the CDC confirm that XMRV is a human virus, and then single-handedly blow all of the negative studies out of the water:http://phoenixrising.me/forums/showthread.php?11415-Switzer-now-finds-(some)-XMRV-in-Prostate-Cancer